Latency and reactivation of a precore mutant hepatitis B virus in a chronically infected patient.
In human patients infected with hepatitis B virus (HBV) seroconversion from HBe to anti-HBe often signals virus elimination. Occasionally, a second viremic phase is observed which may be due to superinfection with a variant or reactivation of a latent virus. To differentiate between these two possibilities we investigated the nucleotide sequences of virus populations from sera of a chronically infected patient who had two distinct viremic phases, one e-antigen positive and one anti-HBe antibody positive. By direct sequencing of amplified HBV C- and pre-S gene sequences we found that the viruses in the two populations differed by only two point mutations, one of which prevents expression of precore derived e-antigen. In the nonviremic phase viral DNA and antigen were found in the liver but nucleocapsid protein expression appeared drastically downregulated. These data demonstrate that HBV can enter a latent phase with low expression of core protein and selection for HBV variants which cannot synthesize e-antigen. This suggests that e-antigen expression can be a critical target for virus elimination and that loss of its expression can prolong chronicity and provoke latency of HBV infection.
Raimondo
G
G
Max-Planck-Institut für Biochemie, Martinsried, Federal Republic of Germany.
Stemler
M
M
Schneider
R
R
Wildner
G
G
Squadrito
G
G
Will
H
H
D000956:Antigens, Viral / Q000032:analysis / Q000276:immunology; D001483:Base Sequence; D002908:Chronic Disease; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D006509:Hepatitis B / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D006513:Hepatitis B e Antigens / Q000235:genetics / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics* / Q000254:growth & development / Q000276:immunology; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011930:Reaction Time / Q000502:physiology*; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism; D014775:Virus Activation
D000956:Antigens, Viral; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D014758:Viral Core Proteins